The oxidation of the catecholamine neurotransmitters on electrodes has been intensively studied because the reaction current through the electrodes can be used to monitor the neurotransmitters in living organisms. This electrochemical method of detecting the neurotransmitters has many advantages over other methods. For example, the electrodes can be made extremely small which can be conveniently implanted in living organisms, and the response time is very fast so that the neurotransmitters can be easily monitored in real-time. However, ordinary electrodes cannot selectively and reproducibly detect the neurotransmitters therefore they are not suitable for practical use. In order to improve the selectivity and reproducibility of the electrodes, various empirical methods have been developed to modify the electrode surfaces. Using modified electrodes, in vivo detection of neurotransmitters of freely moving rats has been recently demonstrated, but the progress has been seriously hindered by the lack of understanding how the modifications improve the electrode performance. Using the scanning (STM), atomic force (AFM) microscopes and other surface analytical techniques, it is now possible to directly visualize and study biochemical reactions on electrodes in aqueous solutions on the molecular scale. The feasibility has been recently demonstrated in this lab by studying the oxidations of several biological molecules in real-time with molecular resolution. In this project, these techniques will be applied to study the oxidation of the catecholamine neurotransmitters on both unmodified and modified electrodes. The objective is to understand how various modifications of electrodes improve the electrode performance as the neurotransmitter sensors. This study will lead us to design more effective sensors for studying the physiological processes of the neurotransmitters and for diagnosing the related diseases (anxiety, depression, parkinsonism, etc.), and it may also provide us with new insights into the biological functions of the catecholamines in living systems. To reach the objective, the following tasks will be performed: (1) characterize the surface structure and chemical composition of both modified and unmodified electrodes; (2) determine how the molecules are adsorbed and arranged on the electrode surfaces; (3) directly monitor the dynamic process of the reaction with molecular resolution; (4) study how the oxidation is affected by the surface structure and chemical compositions of the modified electrodes.